In 2007, Westwick was cast as Chuck Bass in The CW's teen drama series Gossip Girl, based on the book series of the same name by Cecily von Ziegesar. For his portrayal, he assumed an American accent based on the character Carlton Banks from The Fresh Prince of Bel-Air.[4] As a result of the show's success, he was named one of 2008's Sexiest Men Alive by People magazine,[5] appeared the following year on its "100 Most Beautiful" list with the whole cast of Gossip Girl,[6] earned two awards in 2008 and 2009 for Best TV Villain at the Teen Choice Awards, and was named Breakthrough Talent by GQ in 2010.[7]Entertainment Weekly also named Westwick's character Chuck Bass number one in their "Best Dressed TV characters of 2008" list (tied with Leighton Meester's character Blair Waldorf), as well as in their "Best Performances" list alongside co-star Meester.[8] Westwick said: "There wasn't much work in the UK. I was only in LA for a month and I got this show. It's changed my life."[9]

At the 2008 White House Correspondents' Dinner

In 2008, Westwick became the new face of K-Swiss,[10] making him the second member of the Gossip Girl cast to endorse sportswear (Leighton Meester endorsed Reebok)[11] and appeared in the horror film 100 Feet. In 2009, Westwick played a role in the sequel to Donnie Darko and also guest starred in the third season of the Showtime original series Californication as a student who was fascinated with vampire literature.[12] In May 2009, he was attached to play Heathcliff in Wuthering Heights.[13] However, in January 2010 the project passed into the hands of a new director which caused a change in the cast. In 2010, Westwick appeared alongside Dev Patel and Pamela Anderson in the McHenry Brothers short film The Commuter, which was shot on a Nokia N8 smartphone.[14]

Westwick fronted the British indie rock band The Filthy Youth, composed of himself, Ben Allingham, Jimmy Wright, Tom Bastiani, and John Voight.[24] The band, formed in 2006, was inspired by the Rolling Stones, The Doors and Kings of Leon. The songs "Come Flash All You Ladies" and "Orange" were both featured in an episode of Gossip Girl.[25]